The specific aim is to assess the feasibility of immunization against periodontitis using a vaccine against Porphyromonas gingivalis. Three immunization studies have been conducted. In Study 1, 10 control and 10 experimental animals were immunized using the whole-cell vaccine; the results suggest that immunization is safe and effective. Study 2 was a replication of Study 1, this time using 14 control and 14 immunized animals. In Study 3 a purified porphypain-2 vaccine was used in five animals. During the course of these studies none of the immunized animals developed systemic health conditions. Animal weight changes were within normal limits. IgG titers to P.gingivalis showed two peaks, at weeks 6 and 20 after immunization. Control animals showed stable and significantly low titers through the study period. Immunized animals showed a lower presence of P.gingivalis than did control animals. Significantly lower levels of prostaglandin E 2 were found in animals immuniz ed w ith porphypain than in animals immunized with whole cells and in control animals (p<0.01). Levels of prostaglandin E 2 have been associated with bone loss. Radiographs showed that the porphypain-immunized animals had significantly less bone loss associated with experimentally induced periodontitis (p<0.001). These animals also had a significant reduction of the presence of P.gingivalis. Thus, the purified vaccine appears to be more effective than whole-cell vaccine. Funds have been sought to continue these studies (a) to confirm the porphypain immunization results and (b) to develop a human vaccine against periodontitis. FUNDING NIH grants RR00166 and DE08555. Houston, L.S., Lukehart, S.A., Mancl, L., Persson, G.R., and Page, R.C. Vaccination reduces prostaglanding E2 levels and bone loss in experimental periodontal disease. Annu. Mtg. IADR, Nice France, Abstr# 138, 1998. Schlegel-Bregenzer Braham, B., Houston, L., Weinberg, A., and Persson, G.R. Serum titers to Bacteroides forsythus in older subjects. Annu. Mtg. IADR, France, Abstr # 1292, 1998. Houston, L.S., Persson ,G.R., Lantz, M.S., Jeffcoat, M.K., Mancl, L.C., Lukehart, S.A., and Page, R.C. Immunization with Porphyromonas gingivalis cysteine protease attenuates alveolar bone loss. Annu. Mtg. IADR, Vancouver BC. Abstr. # 1511, 1999.